Systematic comparison of methods for determining the in vivo biodistribution of porous nanostructured injectable inorganic particles.
Systematic comparison of methods for determining the in vivo biodistribution of porous nanostructured injectable inorganic particles.
复制标题
确定多孔纳米结构可注射无机颗粒体内生物分布的方法的系统比较。
DOI：
10.1016/j.actbio.2019.08.002
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发表时间：
2019
影响因子：
9.7
通讯作者：
Ferrari,Mauro
中科院分区：
文献类型：
--
作者：
Nizzero,Sara;Li,Feng;Zhang,Guodong;Venuta,Alessandro;Borsoi,Carlotta;Mai,Junhua;Shen,Haifa;Wolfram,Joy;Li,Zheng;Blanco,Elvin;Ferrari,Mauro
由于文献中报道了各种各样的生物分布测量技术，重要的是在相同的颗粒平台上对不同方法获得的结果进行并排比较，以确定不同方法之间的差异，突出优点和缺点，并根据具体应用来指导方法选择。无机纳米粒子(INP)由于其可控的设计、生物相容性和良好的降解动力学，在可注射递送载体的开发中发挥了核心作用。因此，准确测定INP的活体分布是开发和优化这类递送载体的关键。在这项研究中，对光谱(电感耦合等离子体光学发射光谱)、荧光(活体成像系统、共聚焦显微镜和平板阅读器)和基于放射性标记(伽马计数器)的技术进行了系统的比较，以评估小鼠体内生物分布测量的准确性和灵敏度。每种方法都在多孔硅颗粒上进行评估，多孔硅颗粒是一种成熟的、多功能的注射递送平台。对所有主要器官的生物分布进行评估，并根据绝对结果(%ID/g和%ID/器官，如果可能)和敏感性(σ%)进行比较。最后，我们讨论了如何将这些结果扩展到为其他平台和特定应用提供方法选择的信息，并展望了对临床前和临床研究的潜在益处。总之，这项研究为选择能产生定量结果的体内分布方法提供了一个新的实用指南。说明意义这项工作的意义在于使用一个单一的平台来测试不同生物分布方法在体内的性能，并有严格的定量指标。这些结果，结合各种技术的优缺点的定性比较，旨在支持根据具体应用合理选择各种不同的方法，以提高对将来将发表的生物分布结果的定量描述。
With a wide variety of biodistribution measurement techniques reported in the literature, it is important to perform side-by-side comparisons of results obtained with different methods on the same particle platform, to determine differences across methods, highlight advantages and disadvantages, and inform methods selection according to specific applications. Inorganic nanostructured particles (INPs) have gained a central role in the development of injectable delivery vectors thanks to their controllable design, biocompatibility, and favorable degradation kinetic. Thus, accurate determination ofin vivobiodistribution of INPs is a key aspect of developing and optimizing this class of delivery vectors. In this study, a systematic comparison of spectroscopy (inductively coupled plasma optical emission spectroscopy), fluorescence (in vivoimaging system, confocal microscopy, and plate reader), and radiolabeling (gamma counter)-based techniques is performed to assess the accuracy and sensitivity of biodistribution measurements in mice. Each method is evaluated on porous silicon particles, an established and versatile injectable delivery platform. Biodistribution is evaluated in all major organs and compared in terms of absolute results (%ID/g and %ID/organ when possible) and sensitivity (σ%). Finally, we discuss how these results can be extended to inform method selection for other platforms and specific applications, with an outlook to potential benefit for pre-clinical and clinical studies. Overall, this study presents a new practical guide for selection ofin vivobiodistribution methods that yield quantitative results.Statement of SignificanceThe significance of this work lies in the use of a single platform to test performances of different biodistribution methodsin vivo, with a strict quantitative metric. These results, united with the qualitative comparison of advantages and disadvantages of each technique, are aimed at supporting the rational choice of each different method according to the specific application, to improve the quantitative description of biodistribution results that will be published by others in the future.